The long-term goal of this research is development of drugs which would modify pharmacological effects of ethanol on the brain or symptoms of ethanol withdrawal by interaction with cyclic nucleotides. We have reported recently that acute ethanol administration decreases cyclic nucleotides in most brain areas and that during ethanol withdrawal cyclic AMP increases in the cerebral cortex and pons-medulla oblongata, while cyclic GMP levels increase in the cerebellum and pons-medulla oblongata. These findings we further pursued by correlating changes of cyclic nucleotide and GABA levels during ethanol withdrawal. We have found a negative correlation between cyclic GMP and GABA levels in the cerebellum which was also described by others in conditions of increased susceptibility to convulsions. Other correlations indicated a relationship between cyclic GMP levels in the cerebellum and cyclic AMP levels in the pons-medulla oblongata, relationship between cyclic AMP levels in the pons-medulla oblongata and cerebral cortex, and reciprocal relationship of cyclic AMP and cyclic GMP levels in the cerebral cortex. Effects of pilocarpine, which increases cyclic GMP levels, on a startle response were also studied. Results indicate that the ethanol-induced decrease of the startle response is probably not mediated by decreased cyclic GMP levels. Further experiments will analyze variable involved in an acute effect of ethanol on GABA levels using-pyridoxin-deficient rats and evaluating an interaction between ethanol effects and stress. Interaction of ethanol with other drugs affecting cyclic nucleotides will be also studied. BIBLIOGRAPHIC REFERENCES: Volicer, L., Mirin, R. and Gold, B.I.: Effect of acute ethanol administration on the cyclic AMP system in rat brain. J. Studies Alcohol 38: 11-24, 1977. Volicer, L. and Hurter, B.P.: Effect of acute and chronic ethanol administration and withdrawal on adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate levels in the rat brain. J. Pharmacol. Exp. Ther. 200: 298-305, 1977.